I hadn't encountered the "StarFleet Museum" before, so I killed an hour or so browsing around. Some of the designs were interesting, but began to blend together after a while. What eventually kept me going was trying to figure out how the NX01 could possibly fit into their taxonomy of future starship designs.

It can't, and I think that the Enterprise artists chickened out and figured that the audience wouldn't accept a starship named "Enterprise" that didn't follow the Constitution-class body plan.

I think you're right that the Comet design would've been more plausible for an early starship design. The spherical habitation module would be descended from a line of engineering speculation dating back to the 20th century (while the saucer shape is "borrowed forward" from later designs). A sphere offers the best ratio of structural mass to enclosed volume, followed by cylinders...while the saucer has got to be the worst possible shape except maybe for a rectangular pizza box shape. That's why Roddenberry quickly had to invent magic technology like "structural integrity fields" and "inertial dampeners" just to keep the crazy Rube Goldberg design from flying apart the first time the warp engines were lit. Using that design as early as the mid 2100s would require that those technologies already exist, putting the cart definitely before the horse. What else can I criticize? Gee, how about decks parallel to the axis of motion, like an ocean liner, requiring the inertial dampeners to be constantly compensating for even the gentlest maneuvers. TOS would've been easier to film if the actors merely had had to flex their knees in unison instead of coordinating acting like they're being shaken around like rats by an angry terrier. And why was the motion always side-to-side, even when the ship was taking hits from all directions? Sheesh. Or the warp nacelles on the end of spindly pylons...bet the first few test flights ended in disaster when the pylons snapped like toothpicks and the warp engines flew off the to end of the universe. You can go crazy trying to figure out the center of mass in that design, but for sure it's offset from the plane of the engines...what kept the ship from cartwheeling through space?

I should get a grip, it's only a fictional design for a TV show.

As far as storytelling goes, I have to agree, they went off the rails inventing Borg-class threats like the Xindi; and a Temporal War by definition would be/have been taking place throughout all eras of the ST universe. The Xindi are particularly jarring because an event like the attack on Earth would've had reverberations for centuries forward. It would've been mentioned in passing historical references, and in cultural references like "we don't want another Xindi attack", just as "9/11" has become an inextricable part of our culture now. They were on firmer ground exploring themes connected through allusions backward from the TOS and later eras--Vulcans vs. Andorians, war with the Romulans, etc. And even though my first reaction to your reference to "transgenic Humans" was "well of course Lee would be attracted to that story", you're actually right, because it's connected by several historical allusions and to Khan in TOS and the movie. It was clever how they worked in Brent Spiner as Noonian Singh and portrayed how he saw the light and shifted to cybernetics--Spiner gave birth to Data. Kind of illustrates my point about reverberations through time: the "Eugenics Wars" were so significant that they formed the storytelling anchor connecting the 22nd and 20th centuries.

OK, so you liked the Enterprise theme, and I"m thoroughly outnumbered on that score. Oh well, to each his own.